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Ostermayer: Created page with "Hypersensitivity pneumonitis (HP), formerly known as extrinsic allergic alveolitis, is an immune-mediated interstitial lung disease caused by an exaggerated inflammatory response to repeated inhalation of a sensitizing antigen in a susceptible host.Raghu G, et al. Diagnosis of hypersensitivity pneumonitis in adults. An official ATS/JRS/ALAT clinical practice guideline. ''Am J Respir Crit Care Med''. 2020;202(3):e36-e69. More than 300 causative a..."

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Created page with "Hypersensitivity pneumonitis (HP), formerly known as extrinsic allergic alveolitis, is an immune-mediated interstitial lung disease caused by an exaggerated inflammatory response to repeated inhalation of a sensitizing antigen in a susceptible host.<ref name="ATS2020">Raghu G, et al. Diagnosis of hypersensitivity pneumonitis in adults. An official ATS/JRS/ALAT clinical practice guideline. ''Am J Respir Crit Care Med''. 2020;202(3):e36-e69.</ref> More than 300 causative a..."

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Hypersensitivity pneumonitis (HP), formerly known as extrinsic allergic alveolitis, is an immune-mediated interstitial lung disease caused by an exaggerated inflammatory response to repeated inhalation of a sensitizing antigen in a susceptible host.<ref name="ATS2020">Raghu G, et al. Diagnosis of hypersensitivity pneumonitis in adults. An official ATS/JRS/ALAT clinical practice guideline. ''Am J Respir Crit Care Med''. 2020;202(3):e36-e69.</ref> More than 300 causative antigens have been identified.<ref name="ALA">Hypersensitivity Pneumonitis. American Lung Association.</ref> The disease exists on a spectrum from acute self-limiting inflammation to irreversible pulmonary fibrosis indistinguishable from [[idiopathic pulmonary fibrosis]] (IPF). '''Antigen avoidance is the cornerstone of management'''<ref name="StatPearls">Hypersensitivity Pneumonitis. ''StatPearls''. NCBI Bookshelf. Updated July 2023.</ref> — the ED physician's most important role is to consider the diagnosis, obtain a thorough exposure history, and initiate appropriate workup.

==Background==
*Combination of type III (immune complex) and type IV (delayed-type/cell-mediated) hypersensitivity reactions<ref name="StatPearls"/>
*Inflammation is '''bronchiolocentric''' — centered on the small airways due to the inhalational route of injury<ref name="StatPearls"/>
*Pathologic hallmark: '''poorly formed, non-caseating granulomas''' with lymphocytic infiltration around bronchioles (distinct from sarcoidosis, which has well-formed granulomas along the bronchovascular bundle)<ref name="StatPearls"/>
*Cigarette smoking is paradoxically '''protective''' — nicotine inhibits macrophage activation and lymphocyte proliferation; however, smokers who do develop HP tend to have more fibrotic disease<ref name="StatPearls"/>
*Genetic susceptibility through MHC class II (HLA-DR and HLA-DQ) polymorphisms<ref name="StatPearls"/>
*Incidence: ~1–2 per 100,000 person-years; accounts for 1.5–12% of all interstitial lung diseases<ref name="Merck">Hypersensitivity Pneumonitis. ''Merck Manual Professional Edition''. Updated 2025.</ref>
*'''Current classification (ATS/JRS/ALAT 2020):''' Two phenotypes replace the older acute/subacute/chronic terminology<ref name="ATS2020"/>
**'''Non-fibrotic HP:''' Inflammatory, often reversible with antigen avoidance ± corticosteroids
**'''Fibrotic HP:''' Established fibrosis present on imaging or biopsy; worse prognosis; may progress to end-stage lung disease
*'''Common exposures and eponyms:'''
**'''Farmer's lung''' — thermophilic ''Actinomycetes'' (''Saccharopolyspora rectivirgula'') in moldy hay, grain, straw; the prototype of HP<ref name="StatPearls"/>
**'''Bird fancier's lung''' (pigeon breeder's disease) — avian proteins in droppings, feathers, serum; '''most common form of HP worldwide''' (66–68% of all cases); 5-year mortality ~30% (worse prognosis than farmer's lung due to persistent domestic antigen exposure)<ref name="Medscape">Hypersensitivity Pneumonitis. ''Medscape/eMedicine''. Updated 2024.</ref>
**'''Hot tub lung''' — ''Mycobacterium avium'' complex (MAC) in aerosolized warm water; may represent true infection vs. HP (debated)<ref name="Medscape"/>
**'''Humidifier lung''' — ''Thermoactinomyces'', ''Cladosporium'' in contaminated HVAC systems, humidifiers
**'''Chemical worker's lung''' — isocyanates (toluene diisocyanate, MDI), zinc, nickel; low-molecular-weight haptens that form antigenic complexes with host proteins<ref name="Merck"/>
**Others: Mushroom worker's lung, maple bark disease, malt worker's lung (''Aspergillus clavatus''), saxophone lung (''Candida''/''Ulocladium'' in mouthpieces), metalworking fluid HP, cheese worker's lung
**'''Feather bedding HP''' — indirect bird antigen exposure from down pillows and duvets; easily missed on history<ref name="StatPearls"/>
*Farming, bird contact, and water contamination account for ~75% of cases<ref name="Merck"/>

==Clinical Features==
'''Acute/non-fibrotic HP''' (high-dose, intermittent exposure):
*Symptoms begin '''4–8 hours''' after antigen exposure (key historical clue)<ref name="StatPearls"/>
*Fever, chills, malaise, myalgias, dry cough, dyspnea — often misdiagnosed as '''flu-like illness''' or [[pneumonia]]
*Symptoms typically resolve within '''1–2 days''' of avoiding exposure<ref name="StatPearls"/>
*Recurrent stereotyped episodes temporally linked to a specific environment are highly suggestive
*Exam: fever, tachypnea, bibasal '''fine inspiratory crackles'''; wheeze is uncommon<ref name="PatientInfo">Extrinsic Allergic Alveolitis. ''Patient.info''. Updated August 2024.</ref>
*'''Severe acute HP''' can cause life-threatening respiratory failure with cyanosis and respiratory distress at rest<ref name="PatientInfo"/>

'''Chronic/fibrotic HP''' (low-dose, prolonged exposure):
*'''Insidious onset''' of progressive dyspnea, chronic dry cough, fatigue, weight loss<ref name="StatPearls"/>
*Often '''no history of acute episodes''' — the intermittent febrile response may be absent
*No clear temporal link to exposure (antigen exposure may be continuous and low-level)
*Exam: tachypnea, inspiratory crackles (particularly bibasal), '''clubbing in up to 50%''' of chronic cases<ref name="Wikipedia">Hypersensitivity pneumonitis. ''Wikipedia''. Updated September 2025.</ref>
*Late findings: cyanosis, signs of [[pulmonary hypertension]] and right heart failure
*May be clinically and radiologically '''indistinguishable from IPF'''<ref name="ATS2020"/>

'''Key history questions for the ED:'''
*Occupation (farming, bird handling, factory work, metalworking, brewing, woodworking)
*Hobbies (bird keeping, pigeon racing, hot tub use, gardening/composting)
*Home environment (feather bedding/pillows, visible mold, water damage, humidifiers, HVAC maintenance, pet birds, indoor hot tub)
*Timing of symptoms relative to specific environments — '''do symptoms improve on weekends, vacations, or hospitalizations?'''
*New exposures (recently acquired birds, new home, new workplace, CPAP/BiPAP equipment)

==Differential Diagnosis==
'''Acute HP differential:'''
*[[Pneumonia]] (community-acquired — the most common initial misdiagnosis)
*[[Influenza]] and other viral respiratory infections
*'''Organic dust toxic syndrome (ODTS)''' — '''the critical ED differential'''; occurs after heavy organic dust exposure with identical flu-like symptoms; differs from HP because: (1) CXR is '''normal''' (no infiltrates), (2) severe hypoxemia does not occur, (3) '''no prior sensitization required''' (can occur on first exposure), (4) no long-term sequelae; ODTS is '''30–50 times more common''' than farmer's lung<ref name="VonEssen">Von Essen SG, et al. Organic dust toxic syndrome: an acute febrile reaction to organic dust exposure distinct from hypersensitivity pneumonitis. ''Clin Toxicol''. 1990;28(4):389-420.</ref>
*Metal fume fever (zinc, copper exposure — similar flu-like presentation hours after exposure)
*Inhalation fever (self-limited; no CXR infiltrates; no sequelae)<ref name="Medscape"/>
*[[Silo filler's disease]] (nitrogen dioxide exposure — distinct toxicant, different mechanism)
*[[Pulmonary embolism]]

'''Chronic HP differential:'''
*[[Idiopathic pulmonary fibrosis]] (UIP pattern; '''basal predominant'''; no exposure history; no granulomas; no air trapping)
*[[Sarcoidosis]] (well-formed granulomas; hilar lymphadenopathy prominent on CXR; non-caseating but along bronchovascular bundle, not bronchiolocentric)<ref name="StatPearls"/>
*Non-specific interstitial pneumonia (NSIP)
*Cryptogenic organizing pneumonia (COP/BOOP)
*[[Bronchiolitis obliterans]]
*Connective tissue disease–associated ILD
*Drug-induced pneumonitis ([[methotrexate]], [[amiodarone]], [[nitrofurantoin]], [[bleomycin]])
*[[Tuberculosis]] (caseating granulomas; positive AFB)
*Lymphocytic interstitial pneumonia (LIP)
*Allergic bronchopulmonary aspergillosis (ABPA)

{{Template:SOB DDX}}

==Evaluation==
===Workup===
'''Laboratory (ED):'''
*CBC: leukocytosis with '''left shift and neutrophilia''' in acute HP; eosinophilia is NOT typical (its presence suggests ABPA, eosinophilic pneumonia, or parasitic disease)
*[[CRP]]/[[ESR]]: elevated in acute HP
*[[Basic metabolic panel]], lactate
*ABG/VBG: hypoxemia; may show widened A-a gradient; severe acute HP can cause significant respiratory failure
*Procalcitonin: may help differentiate from bacterial [[pneumonia]] (often low in HP, elevated in bacterial infection)
*'''Serum-specific IgG antibodies (precipitins):''' NOT an ED test, but understand their limitations — positive results reflect '''exposure/sensitization, not necessarily disease''' (~40% of pigeon breeders have positive IgG without clinical HP); false negatives are common because the offending antigen may not be in the test panel<ref name="EMCrit">Hypersensitivity Pneumonitis (HP). ''EMCrit/IBCC''. Updated August 2025.</ref>

'''Imaging:'''

''Chest X-ray:''
*Acute HP: diffuse '''bilateral reticulonodular''' or ground-glass infiltrates; may be normal in mild disease<ref name="Medscape"/>
*Chronic HP: reticulonodular pattern, fibrotic changes, volume loss (upper/mid-zone predominance may help distinguish from IPF)
*'''ODTS:''' CXR is '''normal''' — this is the key imaging distinction from acute HP<ref name="VonEssen"/>

''High-resolution CT (HRCT) — the key imaging study:''

''Non-fibrotic HP:''
*'''Profuse ground-glass centrilobular nodules''' — often described as "fluffy" or "rosette" pattern; '''essentially diagnostic''' in the appropriate clinical context<ref name="EMCrit"/>
*Diffuse ground-glass opacities
*Air trapping on expiratory images (mosaic attenuation)
*Upper/mid-lung predominance (unlike IPF which is basal-predominant)

''Fibrotic HP:''
*Reticular pattern, traction bronchiectasis, honeycombing (but honeycombing is usually minimal and '''not basal-predominant''' unlike IPF)
*'''Three-density pattern''' (previously called "head cheese sign"): coexisting areas of ground-glass opacity, normal lung, and air trapping (low attenuation) — '''highly suggestive of fibrotic HP over IPF'''<ref name="ATS2020"/>
*Air trapping on expiratory CT in ≥3 lobes bilaterally is '''inconsistent with IPF''' and favors HP<ref name="EMCrit"/>
*Upper/mid-zone fibrosis (vs. basal in UIP/IPF)
*Centrilobular nodules may still be visible (~50% of cases)<ref name="EMCrit"/>
*Mild mediastinal lymphadenopathy may occur (usually <15 mm, 1–2 nodes)<ref name="EMCrit"/>

'''Pulmonary function tests''' (not performed in ED, but understand the pattern):
*Classically '''restrictive''' pattern (reduced FVC, reduced TLC) with reduced DLCO<ref name="StatPearls"/>
*May also show '''obstructive''' or '''mixed''' pattern (especially with air trapping component)
*Reduced DLCO is common in both fibrotic and non-fibrotic HP

'''Bronchoalveolar lavage (BAL)''' (outpatient/inpatient — not ED):
*'''Lymphocytosis''' (often >50%) with '''low CD4:CD8 ratio''' supports HP<ref name="StatPearls"/>
*Helps distinguish from sarcoidosis (normal cell count, high CD4:CD8) and IPF (neutrophilia, not lymphocytosis)
*Lymphocytosis may be absent in chronic/fibrotic HP<ref name="StatPearls"/>

===Diagnosis===
*'''No single test is diagnostic''' — HP requires integration of clinical history, exposure assessment, imaging, and sometimes BAL and/or biopsy through '''multidisciplinary discussion (MDD)'''<ref name="ATS2020"/>
*The 2020 ATS/JRS/ALAT guideline provides a diagnostic confidence framework combining: (1) identified exposure, (2) characteristic HRCT pattern, (3) BAL lymphocytosis, and (4) histopathology when needed<ref name="ATS2020"/>
*'''In the ED, focus on:'''
**(1) Recognizing the clinical pattern — recurrent flu-like illness temporally linked to specific environments, or progressive ILD with exposure history
**(2) Obtaining a '''thorough exposure history''' (occupation, hobbies, home environment, pets, bedding, hot tubs, HVAC)
**(3) Ordering HRCT (or at minimum CXR) and basic labs
**(4) Communicating suspicion to the admitting team or arranging outpatient pulmonology referral
*Surgical lung biopsy is reserved for cases where confident diagnosis cannot be reached after clinical evaluation, imaging, and BAL<ref name="ATS2020"/>
*Transbronchial cryobiopsy is increasingly used as a less invasive alternative with reasonable yield<ref name="ATS2020"/>

==Management==
'''1. Antigen avoidance — the single most important intervention'''<ref name="StatPearls"/>
*Identify and eliminate the causative exposure
*Occupational: workplace modification, personal protective equipment (N95 mask), job change if necessary
*Domestic: remove birds, replace feather bedding, remediate mold/water damage, clean or replace HVAC systems and humidifiers, maintain hot tubs properly
*'''Nonfibrotic HP is often fully reversible''' if antigen exposure is eliminated early<ref name="StatPearls"/>

'''2. Corticosteroids — hasten recovery but do not change long-term prognosis if exposure continues'''<ref name="StatPearls"/>
*'''Acute HP:''' Prednisone 0.5–1 mg/kg/day for 1–2 weeks, then taper<ref name="Medscape2">Hypersensitivity Pneumonitis Treatment. ''Medscape/eMedicine''. Updated 2024.</ref>
*'''Subacute/chronic HP:''' Prednisone 0.5–1 mg/kg/day for 4–8 weeks, then gradual taper to maintenance ~10 mg/day or off, guided by clinical response and PFTs<ref name="Medscape2"/>
*Note: '''No randomized controlled trials''' demonstrate long-term benefit of corticosteroids in HP; they improve short-term lung function but without antigen avoidance, disease will recur<ref name="StatPearls"/>
*'''Mild acute HP may resolve spontaneously''' with antigen avoidance alone — corticosteroids are not always required

'''3. ED management of acute presentation:'''
*Supplemental O2 to maintain SpO2 >92%
*Corticosteroids if moderate-to-severe respiratory impairment (methylprednisolone IV or prednisone PO)
*Consider empiric antibiotics pending workup if [[pneumonia]] cannot be excluded (HP and infection are often indistinguishable early)
*Do NOT dismiss recurrent "flu-like illness" in a farmer, bird keeper, or hot tub user — '''ask about exposure history and symptom timing'''

'''4. Outpatient management (coordinate with pulmonology):'''
*'''Steroid-sparing immunosuppression''' for chronic HP with ongoing inflammation: mycophenolate mofetil or azathioprine<ref name="ERJ">Costabel U, et al. Diagnosis, course and management of hypersensitivity pneumonitis. ''Eur Respir Rev''. 2022;31(163):210169.</ref>
*'''Antifibrotic therapy''' for progressive fibrotic HP (progressive pulmonary fibrosis phenotype): nintedanib (INBUILD trial) slows FVC decline; pirfenidone is an alternative<ref name="Merck"/>
*PCP prophylaxis should be considered for patients on dual immunosuppression or >20 mg prednisone chronically<ref name="AJRCCM2017">Salisbury ML, et al. Diagnosis and treatment of fibrotic hypersensitivity pneumonia. ''Am J Respir Crit Care Med''. 2017;196(6):690-699.</ref>
*Pulmonary rehabilitation, supplemental O2 as needed
*Lung transplantation for end-stage fibrotic HP refractory to all therapy

==Disposition==
*'''Admit:'''
**Respiratory failure or significant hypoxemia (new O2 requirement)
**Severe acute HP with high fever, tachypnea, and respiratory distress
**Diagnostic uncertainty — cannot exclude [[pneumonia]], [[pulmonary embolism]], or other life-threatening cause
**Known HP with acute exacerbation not responding to initial treatment
**Chronic HP with acute deterioration in functional status
*'''Discharge with close follow-up:'''
**Mild acute HP with adequate oxygenation, improving on corticosteroids, and identifiable antigen source that can be immediately avoided
**Suspected HP with stable vital signs and adequate oxygenation — arrange:
***HRCT if not performed in ED
***Outpatient pulmonology referral within 1–2 weeks
***Outpatient PFTs
**'''Specific discharge counseling:'''
***'''Identify and avoid the exposure''' — this is the most important instruction
***Return for worsening dyspnea, fever, or inability to maintain oral intake
***Do not return to the implicated environment (barn, bird room, workplace, hot tub) until seen by pulmonology
***Begin prednisone taper if prescribed, with PCP follow-up for monitoring

==See Also==
*[[Bronchiolitis obliterans]]
*[[Idiopathic pulmonary fibrosis]]
*[[Sarcoidosis]]
*[[Pneumonia]]
*[[Smoke inhalation]]
*[[Asthma]]
*[[Occupational asthma]]
*[[Eosinophilic pneumonia]]

==External Links==
*[https://www.ncbi.nlm.nih.gov/books/NBK499918/ Hypersensitivity Pneumonitis — StatPearls]
*[https://emcrit.org/ibcc/hp/ Hypersensitivity Pneumonitis — EMCrit/IBCC]
*[https://www.atsjournals.org/doi/full/10.1164/rccm.202005-2032ST ATS/JRS/ALAT Clinical Practice Guideline: Diagnosis of HP (2020)]
*[https://www.merckmanuals.com/professional/pulmonary-disorders/interstitial-lung-diseases/hypersensitivity-pneumonitis Hypersensitivity Pneumonitis — Merck Manual Professional]
*[https://www.lung.org/lung-health-diseases/lung-disease-lookup/hypersensitivity-pneumonitis/learn-about-hypersensitivity Hypersensitivity Pneumonitis — American Lung Association]
*[https://publications.ersnet.org/content/errev/31/163/210169 Diagnosis, Course and Management of HP — European Respiratory Review (2022)]

==References==
<references/>

[[Category:Pulmonary]]

Hypersensitivity pneumonitis - Revision history

Danbot: Strip excess bold

Danbot: Moved intro into Background as bullets; removed excessive bold from bullet lead-ins; added Pulmonary fibrosis differential and Cough DDX templates